Pyrogenicity caused by the Gram-negative bacterial endotoxins has always been a serious problem in the plasma fractionation industry. Many a time, manufacturers find their final product pyrogenic prior to filling thus resulting in the loss of the entire lot of valuable material. It has been known for 30 years that normal human plasma (or serum) has the ability to diminish the pyrogenicity of endotoxins derived from Gram-negative bacteria. The long-term objective of this research proposal, therefore, is to develop a large scale procedure for the isolation from human plasma of this inactivator. It could then be added to depyrogenate those pyrogenic blood products such as albumin, immune globulin, antihemophilic factor (AHF), Factor IX, interferons, and other biologics thus rendering them suitable again for clinical use. A small scale procedure employing conventional techniques for the isolation of this inactivator in milligram quantities has been developed. During the ensuing 12 months, studies will be initiated to evaluate its feasibility for scaling up without interfering with the routine plasma fractionation, and/or an alternative approach using a one-step affinity adsorption will also be attempted. A decision could then be made as to which is the better procedure in terms of scaling up, purity, yield and stability of the product, and its comformability with the licensing requirements of the Office of Biologics.